罕见脑桥小脑发育不全家系临床研究及遗传学分析

A clinical and genetic study of a rare pontocerebellar hypoplasia family

目的通过对一个脑桥小脑发育不全(PCH)家系的临床和基因进行研究,探讨它的临床特点及致病基因。方法对一个脑桥小脑发育不全的家系成员进行临床资料的收集,绘制遗传系谱图,进行认知、脑电、头颅磁共振及全外显子组测序分析,筛选出相关的基因突变,然后对其进行Sanger测序,进行验证。结果该家系成员中除先证者及其弟,其他成员没有类似疾患表现。先证者及其弟发病年龄、发病症状及神经系统查体结果相似。全外显子组测序:(1)未能发现该疾病已知的相关基因突变;(2)未能筛选出临床表型与遗传方式相匹配的突变基因作Sanger测序;(3)发现了1个基因突变,符合常染色体隐性遗传,但是否与该疾病相关,有待进一步的研究。结论脑桥小脑发育不全可能有新的基因表达类型。

Objective To further explore the clinical characteristics and genetic pathogenesis of pontocerebellar hypoplasia（ PCH）,a PCH family was studied concerning clinical and genetic analysis. Methods The clinical data including clinical characteristics,cognitive function,electroencephalogram（ EEG）,magnetic resonance imaging（ MRI） were collected and the family pedigree tree was drawn. On the other hand,whole-exome sequencing（ WES） was conducted to screen the mutant gene which would be on Sanger sequencing to clarify whether a novel gene mutation could be found and its association with clinical features. Results Except for the proband and his brother,no other family member was affected with such disease. The proband had clinical features consistent with his brother in onset age,clinical presentations,neurological examinations. The WES revealed one gene mutation consistent with autosomal recessive inheritance. Further study should be conducted to check whether it had relationship with the disease.（1）We failed to find the known pathogenic genes.（2）We failed to select the genes mutant which would be consistent with clinical phenotype and inheritance pattern for Sanger sequencing.（3）We found a mutant gene which was consistent with autosomal recessive inheritance,but further study was of necessity to clarify whether it was the pathogenic gene of the disease. Conclusion This study shows that there may be a new mutant gene in potocerebellar hypoplasia.